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Article ; Online: Randomized Trial of Effect of Bariatric Surgery on Blood Pressure After 5 Years.

Schiavon, Carlos A / Cavalcanti, Alexandre B / Oliveira, Juliana D / Machado, Rachel H V / Santucci, Eliana V / Santos, Renato N / Oliveira, Julia S / Damiani, Lucas P / Junqueira, Débora / Halpern, Helio / Monteiro, Frederico de L J / Noujaim, Patricia M / Cohen, Ricardo V / de Sousa, Marcio G / Bortolotto, Luiz A / Berwanger, Otavio / Drager, Luciano F

Journal of the American College of Cardiology

2023 Volume 83, Issue 6, Page(s) 637–648

Abstract: Background: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality.: Objectives: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension ... ...

Abstract	Background: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. Objectives: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. Methods: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. Results: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m Conclusions: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).
MeSH term(s)	Humans ; Female ; Adult ; Middle Aged ; Male ; Blood Pressure ; Antihypertensive Agents/therapeutic use ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/surgery ; Diabetes Mellitus, Type 2/drug therapy ; Bariatric Surgery ; Obesity/complications ; Obesity/surgery ; Gastric Bypass/adverse effects ; Gastric Bypass/methods ; Hypertension/drug therapy ; Hypertension/epidemiology ; Risk Factors ; Treatment Outcome ; Obesity, Morbid/surgery
Chemical Substances	Antihypertensive Agents
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2023.11.032
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Article: Editorial: Metabolic regulation of gamete function in health and disease.

Cohen, Débora J / Da Ros, Vanina G / Brukman, Nicolas G / Amargant, Farners

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 1040708

Language	English
Publishing date	2022-10-19
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.1040708
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Article: Ether lipids and a peroxisomal riddle in sperm.

Horta Remedios, Mayrene / Liang, Weisheng / González, Lucas N / Li, Victoria / Da Ros, Vanina G / Cohen, Débora J / Zaremberg, Vanina

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1166232

Abstract: Sperm are terminally differentiated cells that lack most of the membranous organelles, resulting in a high abundance of ether glycerolipids found across different species. Ether lipids include plasmalogens, platelet activating factor, GPI-anchors and ... ...

Abstract	Sperm are terminally differentiated cells that lack most of the membranous organelles, resulting in a high abundance of ether glycerolipids found across different species. Ether lipids include plasmalogens, platelet activating factor, GPI-anchors and seminolipid. These lipids play important roles in sperm function and performance, and thus are of special interest as potential fertility markers and therapeutic targets. In the present article, we first review the existing knowledge on the relevance of the different types of ether lipids for sperm production, maturation and function. To further understand ether-lipid metabolism in sperm, we then query available proteomic data from highly purified sperm, and produce a map of metabolic steps retained in these cells. Our analysis pinpoints the presence of a truncated ether lipid biosynthetic pathway that would be competent for the production of precursors through the initial peroxisomal core steps, but devoid of subsequent microsomal enzymes responsible for the final synthesis of all complex ether-lipids. Despite the widely accepted notion that sperm lack peroxisomes, the thorough analysis of published data conducted herein identifies nearly 70% of all known peroxisomal resident proteins as part of the sperm proteome. In view of this, we highlight open questions related to lipid metabolism and possible peroxisomal functions in sperm. We propose a repurposed role for the truncated peroxisomal ether-lipid pathway in detoxification of products from oxidative stress, which is known to critically influence sperm function. The likely presence of a peroxisomal-derived remnant compartment that could act as a sink for toxic fatty alcohols and fatty aldehydes generated by mitochondrial activity is discussed. With this perspective, our review provides a comprehensive metabolic map associated with ether-lipids and peroxisomal-related functions in sperm and offers new insights into potentially relevant antioxidant mechanisms that warrant further research.
Language	English
Publishing date	2023-05-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1166232
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Article ; Online: Ether lipids and a peroxisomal riddle in sperm

Mayrene Horta Remedios / Weisheng Liang / Lucas N. González / Victoria Li / Vanina G. Da Ros / Débora J. Cohen / Vanina Zaremberg

Frontiers in Cell and Developmental Biology, Vol

2023 Volume 11

Abstract	Sperm are terminally differentiated cells that lack most of the membranous organelles, resulting in a high abundance of ether glycerolipids found across different species. Ether lipids include plasmalogens, platelet activating factor, GPI-anchors and seminolipid. These lipids play important roles in sperm function and performance, and thus are of special interest as potential fertility markers and therapeutic targets. In the present article, we first review the existing knowledge on the relevance of the different types of ether lipids for sperm production, maturation and function. To further understand ether-lipid metabolism in sperm, we then query available proteomic data from highly purified sperm, and produce a map of metabolic steps retained in these cells. Our analysis pinpoints the presence of a truncated ether lipid biosynthetic pathway that would be competent for the production of precursors through the initial peroxisomal core steps, but devoid of subsequent microsomal enzymes responsible for the final synthesis of all complex ether-lipids. Despite the widely accepted notion that sperm lack peroxisomes, the thorough analysis of published data conducted herein identifies nearly 70% of all known peroxisomal resident proteins as part of the sperm proteome. In view of this, we highlight open questions related to lipid metabolism and possible peroxisomal functions in sperm. We propose a repurposed role for the truncated peroxisomal ether-lipid pathway in detoxification of products from oxidative stress, which is known to critically influence sperm function. The likely presence of a peroxisomal-derived remnant compartment that could act as a sink for toxic fatty alcohols and fatty aldehydes generated by mitochondrial activity is discussed. With this perspective, our review provides a comprehensive metabolic map associated with ether-lipids and peroxisomal-related functions in sperm and offers new insights into potentially relevant antioxidant mechanisms that warrant further research.
Keywords	sperm ; ether lipid ; peroxisome ; metabolism ; oxidative stress ; fertility ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Lifetime burden of disease due to incident tuberculosis: a global reappraisal including post-tuberculosis sequelae.

Menzies, Nicolas A / Quaife, Matthew / Allwood, Brian W / Byrne, Anthony L / Coussens, Anna K / Harries, Anthony D / Marx, Florian M / Meghji, Jamilah / Pedrazzoli, Debora / Salomon, Joshua A / Sweeney, Sedona / van Kampen, Sanne C / Wallis, Robert S / Houben, Rein M G J / Cohen, Ted

The Lancet. Global health

2021 Volume 9, Issue 12, Page(s) e1679–e1687

Abstract: Background: Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore ... ...

Abstract	Background: Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality. Methods: We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease. Findings: Globally, we estimated 122 (95% uncertainty interval [UI] 98-151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38-83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37-57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0-14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6-7·0) were from the disease episode and 5·8 DALYs (3·8-8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23-34) accruing 15 or more years after incident tuberculosis. Interpretation: Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue. Funding: National Institutes of Health.
MeSH term(s)	Cost of Illness ; Disabled Persons/statistics & numerical data ; Female ; Global Burden of Disease/trends ; Global Health ; Humans ; Male ; Quality-Adjusted Life Years ; Risk Factors ; Survivors/statistics & numerical data ; Tuberculosis/epidemiology ; Tuberculosis/rehabilitation
Language	English
Publishing date	2021-12-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2723488-5
ISSN	2214-109X ; 2214-109X
ISSN (online)	2214-109X
ISSN	2214-109X
DOI	10.1016/S2214-109X(21)00367-3
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Article: Low Doses of Glyphosate/Roundup Alter Blood-Testis Barrier Integrity in Juvenile Rats.

Gorga, Agostina / Rindone, Gustavo Marcelo / Centola, Cecilia Lucía / Sobarzo, Cristian M / Pellizzari, Eliana Herminia / Camberos, María Del Carmen / Marín-Briggiler, Clara Isabel / Cohen, Debora J / Riera, Maria Fernanda / Galardo, Maria Noel / Meroni, Silvina Beatriz

Frontiers in endocrinology

2021 Volume 12, Page(s) 615678

Abstract: It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function ... ...

Abstract	It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.
MeSH term(s)	Animals ; Blood-Testis Barrier/drug effects ; Blood-Testis Barrier/metabolism ; Claudins/metabolism ; Connexins/metabolism ; Glycine/administration & dosage ; Glycine/analogs & derivatives ; Herbicides/administration & dosage ; Male ; Occludin/metabolism ; Rats ; Sperm Motility/drug effects ; Spermatogenesis/drug effects ; Spermatozoa/drug effects ; Spermatozoa/metabolism ; Testis/drug effects ; Testis/metabolism ; Testosterone/metabolism ; Thiobarbituric Acid Reactive Substances/metabolism ; Glyphosate
Chemical Substances	Claudins ; Cldn11 protein, rat ; Connexins ; Herbicides ; Occludin ; Thiobarbituric Acid Reactive Substances ; Testosterone (3XMK78S47O) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2021-03-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.615678
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Article ; Online: Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment.

Taieb, Julien / Svrcek, Magali / Cohen, Romain / Basile, Debora / Tougeron, David / Phelip, Jean-Marc

European journal of cancer (Oxford, England : 1990)

2022 Volume 175, Page(s) 136–157

Abstract: Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and occurs in15% of non-metastatic diseases and 5% in the metastatic setting. Nearly 30% of MSI CRCs occur in a context of constitutional mutation of ... ...

Abstract	Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and occurs in15% of non-metastatic diseases and 5% in the metastatic setting. Nearly 30% of MSI CRCs occur in a context of constitutional mutation of the MMR system (Lynch syndrome). Others are sporadic cancers linked to a hypermethylation of the MLH-1 promoter. The pathogenic alterations of MMR genes lead to the accumulation of frequent somatic mutational events and these tumours arbour a high antigen burden and are highly infiltrated with cytotoxic T-cell lymphocytes. Microsatellite instability/DNA mismatch repair deficiency (MSI/dMMR) status has prognostic and predictive implications in non-metastatic and metastatic CRCs. The prognostic value of MSI status in non-metastatic CRCs has been studied extensively, yet the data are more limited for its predictive value in terms of adjuvant chemotherapy efficacy. In both cases (metastatic and non-metastatic settings) treatment with immune check-point inhibitors (ICIs) have shown a remarkable effectiveness in the context of MSI/dMMR status. Indeed, recent data from prospective cohorts and randomised trials have shown a dramatical improvement of survival with immunotherapy (programmed death-ligand 1 [PD-(L)1] cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] blockage) in metastatic or non-metastatic MSI/dMMR CRC. In this review we report and discuss how and for whom to test for the MSI/dMMR phenotype, as well as the prognostic value of this phenotype and the new treatment recommendations options for this unique CRC population. Despite their efficacy, primary and secondary resistance to immune checkpoint inhibitors (ICIs) are observed in more than 50% MSI-H/dMMR CRC patients and in the future how to identify these patients and to overcome resistance will be an important challenge.
MeSH term(s)	Humans ; Brain Neoplasms ; Colonic Neoplasms/drug therapy ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/therapy ; CTLA-4 Antigen/genetics ; DNA ; DNA Mismatch Repair/genetics ; Immune Checkpoint Inhibitors ; Microsatellite Instability ; Microsatellite Repeats ; Neoplastic Syndromes, Hereditary ; Prognosis ; Prospective Studies
Chemical Substances	CTLA-4 Antigen ; DNA (9007-49-2) ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2022-09-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2022.07.020
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article ; Online: Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice.

Silveira Prudente, Arthur / Hoon Lee, Sang / Roh, Jueun / Luckemeyer, Debora D / Cohen, Cinder F / Pertin, Marie / Park, Chul-Kyu / Suter, Marc R / Decosterd, Isabelle / Zhang, Jun-Ming / Ji, Ru-Rong / Berta, Temugin

Brain, behavior, and immunity

2024 Volume 117, Page(s) 51–65

Abstract: Microglia, resident immune cells in the central nervous system, play a role in neuroinflammation and the development of neuropathic pain. We found that the stimulator of interferon genes (STING) is predominantly expressed in spinal microglia and ... ...

Abstract	Microglia, resident immune cells in the central nervous system, play a role in neuroinflammation and the development of neuropathic pain. We found that the stimulator of interferon genes (STING) is predominantly expressed in spinal microglia and upregulated after peripheral nerve injury. However, mechanical allodynia, as a marker of neuropathic pain following peripheral nerve injury, did not require microglial STING expression. In contrast, STING activation by specific agonists (ADU-S100, 35 nmol) significantly alleviated neuropathic pain in male mice, but not female mice. STING activation in female mice leads to increase in proinflammatory cytokines that may counteract the analgesic effect of ADU-S100. Microglial STING expression and type I interferon-ß (IFN-ß) signaling were required for the analgesic effects of STING agonists in male mice. Mechanistically, downstream activation of TANK-binding kinase 1 (TBK1) and the production of IFN-ß, may partly account for the analgesic effect observed. These findings suggest that STING activation in spinal microglia could be a potential therapeutic intervention for neuropathic pain, particularly in males.
MeSH term(s)	Animals ; Female ; Male ; Mice ; Analgesics ; Antibodies ; Microglia ; Neuralgia ; Peripheral Nerve Injuries/complications
Chemical Substances	Analgesics ; Antibodies ; Sting1 protein, mouse
Language	English
Publishing date	2024-01-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2024.01.003
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Compensatory endocytosis occurs after cortical granule exocytosis in mouse eggs.

Gómez-Elías, Matías D / Fissore, Rafael A / Cuasnicú, Patricia S / Cohen, Débora J

Journal of cellular physiology

2019 Volume 235, Issue 5, Page(s) 4351–4360

Abstract: Compensatory endocytosis (CE) is one of the primary mechanisms through which cells maintain their surface area after exocytosis. Considering that in eggs massive exocytosis of cortical granules (CG) takes place after fertilization, the aim of this study ... ...

Abstract	Compensatory endocytosis (CE) is one of the primary mechanisms through which cells maintain their surface area after exocytosis. Considering that in eggs massive exocytosis of cortical granules (CG) takes place after fertilization, the aim of this study was to evaluate the occurrence of CE following cortical exocytosis in mouse eggs. For this purpose, we developed a pulse-chase assay to detect CG membrane internalization. Results showed internalized labeling in SrCl
MeSH term(s)	Animals ; Calcium/metabolism ; Cytoplasmic Granules/metabolism ; Endocytosis/physiology ; Exocytosis/physiology ; Female ; Fertilization/physiology ; Male ; Mice ; Ovum/physiology
Chemical Substances	Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.29311
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Article ; Online: Lifetime burden of disease due to incident tuberculosis

Nicolas A Menzies, PhD / Matthew Quaife, PhD / Brian W Allwood, PhD / Anthony L Byrne, PhD / Anna K Coussens, PhD / Anthony D Harries, ProfMD / Florian M Marx, PhD / Jamilah Meghji, PhD / Debora Pedrazzoli, PhD / Joshua A Salomon, ProfPhD / Sedona Sweeney, PhD / Sanne C van Kampen, PhD / Robert S Wallis, ProfMD / Rein M G J Houben, PhD / Ted Cohen, ProfDPH

The Lancet Global Health, Vol 9, Iss 12, Pp e1679-e

a global reappraisal including post-tuberculosis sequelae

2021 Volume 1687

Abstract: Summary: Background: Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We ... ...

Abstract	Summary: Background: Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality. Methods: We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease. Findings: Globally, we estimated 122 (95% uncertainty interval [UI] 98–151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38–83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37–57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0–14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6–7·0) were from the disease episode and 5·8 DALYs (3·8–8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23–34) accruing 15 or more years after incident tuberculosis. Interpretation: Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue. Funding: National Institutes of Health.
Keywords	Public aspects of medicine ; RA1-1270
Subject code	630
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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